Erythromycin is generally considered compatible with pregnancy and breastfeeding: its base, stearate and ethylsuccinate forms have decades of use, were rated FDA Category B, and are judged acceptable during lactation. The important exceptions are that erythromycin estolate is contraindicated in pregnancy, some observational studies have raised questions about first-trimester macrolide exposure, and for many pregnancy indications azithromycin has now replaced erythromycin as the preferred macrolide.
This page expands on the pregnancy section of our safety overview. For general tolerability see erythromycin side effects.
- Legacy FDA category
- B (base, stearate, ethylsuccinate)
- Contraindicated salt
- Estolate — risk of cholestatic hepatitis in pregnancy
- Main obstetric use
- PPROM latency antibiotics (azithromycin often substituted)
- Group B strep prophylaxis
- No longer recommended (resistance)
- Breastfeeding
- Acceptable; monitor infant
- Newborns
- 0.5% eye ointment once at birth; oral use in early weeks linked to IHPS
Pregnancy Safety Data
FDA Category B and the PLLR
Under the former FDA letter system, erythromycin (other than estolate) was Category B: reproduction studies in animals showed no evidence of fetal harm, but adequate controlled human studies were lacking. In 2015 the FDA's Pregnancy and Lactation Labeling Rule (PLLR) began replacing letter categories with narrative summaries of human and animal data and clinical considerations. Older erythromycin labels still show the letter, and many references continue to quote it. Erythromycin crosses the placenta, but fetal blood levels are low compared with maternal levels.
Questions About First-Trimester Macrolide Use
Because macrolides are widely prescribed, several large observational studies have looked for links with birth defects. A 2020 UK population-based cohort study published in The BMJ (Fan and colleagues) compared children whose mothers were prescribed macrolides with those prescribed penicillins during pregnancy. It reported that first-trimester macrolide prescribing was associated with a higher risk of major malformations, particularly cardiovascular malformations, and that an association was seen for erythromycin specifically. Earlier Swedish registry analyses had raised a similar signal for erythromycin and cardiac defects.
These findings should be interpreted carefully. They come from observational data, in which the underlying infection, fever and other differences between women prescribed macrolides and penicillins can influence results; absolute risks remain low; and other cohort studies and meta-analyses have not consistently confirmed an increased risk. No regulator has contraindicated erythromycin in pregnancy on this basis. A reasonable summary is that erythromycin should be used in early pregnancy when there is a clear indication, and that where an equally effective alternative with stronger reassuring data exists (often a penicillin), that may be preferred. Women who have already taken erythromycin in early pregnancy should not be alarmed; they can discuss it with their maternity team.
Why Erythromycin Estolate Is Contraindicated
Erythromycin estolate carries the highest risk of cholestatic hepatitis among erythromycin salts. In a study of pregnant women treated with estolate, a notable proportion developed raised liver enzymes, and some developed clinical hepatotoxicity that resolved after stopping. US labeling therefore contraindicates the estolate salt in pregnancy. Estolate is no longer marketed in many countries, but if a suspension is prescribed in pregnancy, check that it is ethylsuccinate rather than estolate. See formulations and dosing.
Uses of Erythromycin in Pregnancy
Preterm Prelabor Rupture of Membranes (PPROM)
When the membranes rupture before 34 weeks and the pregnancy is managed expectantly, antibiotics prolong the time until delivery (latency) and reduce maternal and neonatal infection. The large ORACLE I trial found erythromycin improved several neonatal outcomes in PPROM, whereas amoxicillin–clavulanate was associated with an increase in necrotizing enterocolitis — one reason amoxicillin–clavulanate is avoided in this setting.
The regimen described by the American College of Obstetricians and Gynecologists (ACOG Practice Bulletin 217) for PPROM before 34 weeks is:
- First 48 hours: IV ampicillin 2 g every 6 hours plus IV erythromycin 250 mg every 6 hours
- Next 5 days: oral amoxicillin 250 mg every 8 hours plus oral erythromycin base 333 mg every 8 hours
Because of erythromycin shortages, GI intolerance and dosing frequency, many units substitute azithromycin (for example a single 1 g oral dose) for erythromycin, an approach ACOG acknowledges as a reasonable alternative. Local protocols vary. By contrast, routine antibiotics are not recommended for preterm labor with intact membranes; long-term follow-up of the companion ORACLE II trial raised concern about outcomes in children exposed to erythromycin in that setting.
Group B Streptococcus: No Longer Recommended
Erythromycin was once an option for intrapartum group B streptococcal (GBS) prophylaxis in penicillin-allergic women. Because GBS resistance to erythromycin is now common, it was removed from CDC recommendations in 2010, and current ACOG guidance does not include it. Penicillin-allergic women at low risk of anaphylaxis generally receive cefazolin; those at high risk receive clindamycin if the isolate is susceptible, or vancomycin otherwise.
Chlamydia in Pregnancy
The CDC 2021 STI Treatment Guidelines recommend azithromycin 1 g orally in a single dose for chlamydia in pregnancy, with amoxicillin 500 mg three times daily for 7 days as the alternative. Erythromycin is no longer listed, mainly because frequent GI side effects reduced adherence. Doxycycline, the preferred treatment outside pregnancy, is avoided in the second and third trimesters. Test-of-cure about four weeks after treatment and retesting within three months are recommended in pregnancy.
Other Uses
Erythromycin may still be chosen in pregnancy for respiratory or skin infections in women with penicillin allergy, and topical erythromycin is one of the acne treatments considered acceptable in pregnancy because systemic absorption is minimal (see erythromycin for acne). Remember that erythromycin raises blood levels of many medicines through CYP3A4 inhibition — review interactions before prescribing.
Erythromycin and Breastfeeding
Erythromycin passes into breast milk in small amounts. The NIH Drugs and Lactation Database (LactMed) considers it acceptable for nursing mothers, and the BNF and NHS also regard it as suitable when needed. Practical points:
- Monitor the infant for loose stools, diaper rash, oral thrush or unusual fussiness, as with any maternal antibiotic.
- Very young infants: some epidemiological studies have suggested a possible association between maternal macrolide use during breastfeeding in the first weeks after birth and infantile hypertrophic pyloric stenosis (IHPS). The evidence is weaker and less consistent than for direct oral dosing of infants. Seek care promptly if a baby develops forceful, projectile vomiting after feeds.
- Topical and eye preparations used by the mother pose negligible risk. If erythromycin is applied to the breast, wipe it off before nursing.
Erythromycin Eye Ointment for Newborns
Erythromycin 0.5% ophthalmic ointment is applied to newborns to prevent gonococcal ophthalmia neonatorum, an eye infection acquired during birth that can rapidly damage the cornea and cause blindness. In the United States, prophylaxis is recommended for all newborns (a USPSTF grade A recommendation) and is required by law in many states; erythromycin is the only agent currently recommended for this purpose there. Some countries, including Canada and the UK, no longer apply it routinely and instead rely on prenatal screening and treatment.
- How it is given: a ribbon of about 1 cm into each lower conjunctival sac, once, ideally within 1 hour of birth. It should not be flushed out afterward. Application can be delayed briefly to allow initial bonding and breastfeeding.
- Effectiveness: it protects against gonococcal eye infection but does not reliably prevent chlamydial conjunctivitis.
- Side effects: temporary eyelid swelling, redness or mild irritation; blurred vision from the ointment, which may briefly affect early eye contact. It is not associated with IHPS.
If a baby does develop chlamydial conjunctivitis or pneumonia, CDC recommends oral erythromycin base or ethylsuccinate 50 mg/kg/day in 4 divided doses for 14 days, with azithromycin 20 mg/kg/day once daily for 3 days as an alternative; infants treated with oral erythromycin should be monitored for IHPS. See erythromycin eye ointment and pediatric dosing.
Erythromycin vs Azithromycin vs Clarithromycin in Pregnancy
| Feature | Erythromycin | Azithromycin | Clarithromycin |
|---|---|---|---|
| Legacy FDA category | B (estolate contraindicated) | B | C |
| Animal data | No fetal harm shown | No fetal harm shown | Adverse fetal effects at high doses in some species |
| Human experience | Extensive, decades of use; some observational signals for first-trimester exposure | Extensive and growing; generally reassuring | More limited; usually avoided unless no alternative |
| Chlamydia in pregnancy (CDC 2021) | Not listed | Recommended (1 g single dose) | Not listed |
| PPROM latency | ACOG regimen component | Common substitute | Not used |
| GI tolerability | Poor | Good | Moderate |
| CYP3A4 interactions | Strong inhibitor | Minimal | Strong inhibitor |
| Breastfeeding | Acceptable | Acceptable | Generally acceptable; less data |
In short, erythromycin and azithromycin are the macrolides of choice in pregnancy, with azithromycin favored for convenience and tolerability, and clarithromycin reserved for situations where the alternatives are unsuitable. More detail: erythromycin vs azithromycin and erythromycin vs clarithromycin.
Frequently Asked Questions
Is erythromycin safe in pregnancy?
Erythromycin base, stearate and ethylsuccinate have been used in pregnancy for decades and were classed as FDA Category B, meaning animal studies showed no harm. Some observational studies have raised questions about first-trimester macrolide use and birth defects, so it is used when clearly indicated, and the estolate salt is contraindicated because of liver toxicity risk in pregnant women.
Is erythromycin or clarithromycin safer in pregnancy?
Erythromycin (excluding estolate) and azithromycin are generally preferred over clarithromycin in pregnancy. Clarithromycin caused fetal harm in some animal studies and its labeling advises against use in pregnancy unless no alternative is appropriate.
Is erythromycin or azithromycin better in pregnancy?
For most uses in pregnancy, azithromycin is now preferred because it is better tolerated and needs fewer doses. CDC recommends azithromycin for chlamydia in pregnancy, and many obstetric units substitute azithromycin for erythromycin in PPROM regimens.
Can I take erythromycin while breastfeeding?
Yes. Only small amounts pass into breast milk and LactMed considers erythromycin acceptable during breastfeeding. Watch the baby for diarrhea, thrush or unusual fussiness, and seek advice if a young infant develops forceful vomiting, because erythromycin has a possible link with pyloric stenosis in the first weeks of life.
Can you use erythromycin eye ointment on a newborn?
Yes. Erythromycin 0.5% ophthalmic ointment is applied once to both eyes shortly after birth to prevent gonococcal eye infection, and it is the standard agent for this in the United States. It may cause brief eye irritation or mild swelling but is not linked to pyloric stenosis.
Why is erythromycin no longer used for group B strep in pregnancy?
Group B streptococci have become frequently resistant to erythromycin, so it was removed from US recommendations for intrapartum GBS prophylaxis. Penicillin-allergic women now receive cefazolin, or clindamycin or vancomycin depending on allergy severity and susceptibility testing.
Is erythromycin used for chlamydia in pregnancy?
Not as a first choice anymore. The CDC 2021 guidelines recommend a single 1 g dose of azithromycin for chlamydia in pregnancy, with amoxicillin as the alternative; erythromycin was dropped largely because of stomach side effects that reduce adherence.
References
- Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187. https://www.cdc.gov/std/treatment-guidelines/
- American College of Obstetricians and Gynecologists. Prelabor Rupture of Membranes. ACOG Practice Bulletin No. 217. Obstet Gynecol. 2020;135(3):e80–e97.
- American College of Obstetricians and Gynecologists. Prevention of Group B Streptococcal Early-Onset Disease in Newborns. ACOG Committee Opinion No. 797. Obstet Gynecol. 2020;135(2):e51–e72.
- Fan H, Gilbert R, O'Callaghan F, Li L. Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study. BMJ. 2020;368:m331.
- Kenyon SL, Taylor DJ, Tarnow-Mordi W; ORACLE Collaborative Group. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. Lancet. 2001;357(9261):979–988.
- US Preventive Services Task Force. Ocular Prophylaxis for Gonococcal Ophthalmia Neonatorum: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;321(4):394–398.
- Drugs and Lactation Database (LactMed): Erythromycin. National Library of Medicine (US).
- Erythromycin prescribing information (Ery-Tab, E.E.S., erythromycin ophthalmic ointment USP 0.5%). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/
Related Topics
Using erythromycin 0.5% ophthalmic ointment in newborns, children and adults.
Weight-based dosing and the IHPS risk in young infants.
How the two macrolides compare on efficacy, tolerability and safety.
Common and serious reactions and what to do about them.